Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies...

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Transcript of Lalfabeto degli odori Anna Menini Neurobiology Sector International School for Advanced Studies...

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L’alfabeto degli odori

Anna Menini

Neurobiology Sector

International School for Advanced Studies

Trieste, Italy

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XC N

cyanide

S HX

thiol

N H 2X

amine

B rX

Halides

Common Odor Compounds

formiates

XO Halcohols

C O O HX

carboxylic acids

X R

O

aldehydes

XO H

O

X H

O

ketones

estersX R

OR

Xalkanes

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What is a transduction process?

A transduction process is how the energy of an external

stimulus is converted into an electrical signal

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Sensory cells convert a stimulus into an electrical response by a

process known as SENSORY TRANSDUCTION

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• 1- IONOTROPIC

2- METABOTROPIC

How many mechanisms of transduction?

C

l

RG

Na+ Ca2+

Ca2+Na

Lightmolecules

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Receptor potential=Generator potential

• The change in membrane potential produced by the stimulus is a graded potential and can be:

• positive or depolarizing

• negative or hyperpolarizing

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Sensory receptor cells

• Some sensory receptor cells have axons and generate action potentials

• Other cells do not generate action potentials

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Scanning electron micrograph of the olfactory epithelium

E. Morrison and R. Costanzo

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1m

Morrison and Costanzo 1990

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Olfactory transduction takes place in the cilia

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R

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R

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How many odorant receptor genes?

1,000 genes

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Nobel Prize in Physiologyor Medicine 2004

• “for their discoveries of odorant receptors and the organization of the olfactory system”

Linda Buck

Richard Axel

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1000 recettori

350 recettori

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How many type of odorant receptor per cell?

1 type only

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How are odorant receptors spatially expressed in the

olfactory epithelium?

Randomly in each of four zones

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How many odorant molecules can activate an olfactory sensory

neuron ?

One neuron can respond to many odorant molecules

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One type of odorant molecule: how many types of odorant

receptors can activate?

One type of odorant molecule can activate many types of

odorant receptors

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PERA

BANANA

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Denis

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A P B N O C D U G I R F P

DA IN

P U F

P O RD

B UA P

NA U

B N IC

Denis

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From olfactory epithelium to olfactory bulb

Representation of olfactory information

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Mori et al., 1999

Zonal Organization in the Olfactory System

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GLOMERULI

Un certo odore attiva una definita combinazione di glomeruli

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NASO BULBO

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Information coding in the olfactory cortex

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BulbEpithelium Cortex

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NASO BULBO CORTECCIA

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Olfactory transduction cAMP is

the main second messenger

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Ca concentration increases in the ciliaand has a dual effect

1- excitatory2- inhibitory

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Ca excitatory effect:direct activation of Cl current

In situ Cl gradient measurements (rat, mucus/knob concentrations)

[Cl-]i = 69 mM[Cl-]o = 55 mM

Ecl = +6mV(Reuter et al.)

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Adaptation

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Adaptation

• Adaptation adjusts the dynamic range of the response to allow the sensory cell to respond to changes in odor concentration over a wide range.

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Mechanism of adaptation

• Intracellular Calcium concentration controls adaptation acting on the transduction cascade

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Transduction in an olfactory sensory neuron

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Caged compound

Uncaged:physiologically active

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8-Bromo-cAMP

1- is resistant to hydrolysis by PDE

2- activates cAMP-gated channels with higher affinity than cAMP

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Transduction in an olfactory sensory neuron

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S.I.S.S.A. Trieste

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Collaborators

C.N.R. GenovaCristiana PiccoPaola Gavazzo

S.I.S.S.A. TriesteLaura LagostenaAnna BoccaccioAndrea MazzatentaGiulietta PinatoSimone PifferiRanken Shimazaki

JapanTakashi Kurahashi

GermanyBenjamin Kaupp

USAStuart FiresteinPeter Mombaerts